Is MAN2B2 p.Phe329fs (c.984del) pathogenic?

MAN2B2 p.Phe329fs (c.984del) is classified Uncertain significance in MAN2B2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-06). Rare (popmax 0.963%, eas).

How common is MAN2B2 p.Phe329fs (c.984del) in the general population?

MAN2B2 p.Phe329fs (c.984del) is rare (popmax 0.963%, eas) (gnomAD).

MAN2B2 p.Phe329fs

c.984del · rs3216941 · VCV3051657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.963%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	GERP -1.4, phastCons 1
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.963% East Asian · 432/44,880 alleles

Filtering AF 0.888% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.858%

Overall 0.0286% 462/1,613,444 alleles · rare exomes 413/1,461,206 · genomes 49/152,238 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.963%	104
Remaining individualsnot grpmax-eligible	0.0176%	5,681
South Asian	0.0165%	6,070
Admixed American	0.00167%	60,012
European (non-Finnish)	0.000254%	393,321

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MAN2B2
Protein: p.Phe329fs
Coding: c.984del
MANE Select: NM_015274
dbSNP: rs3216941
Type: Deletion
Location: chr4:6594659 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.55

Full MAN2B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAN2B2 p.Ala274fs Uncertain significance ★ same type
MAN2B2 p.Pro883fs Uncertain significance ★ same type
MAN2B2 p.Ser147del Uncertain significance same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/man2b2-p-phe329fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown